Prevention Of Kidney Stones Research Articles

Mechanism of Calcium Oxalate Monohydrate Kidney Stones Formation: Layered Spherulitic Growth

The morphology of calcium oxalate monohydrate (COM) kidney stones is studied using polarized light microscopy and X-ray diffraction. We show that polycrystalline structure of COM stones exhibits spherulitic texture where the arrangement of crystallites indicates that their fast growth direction is perpendicular to the corresponding radius of spherulite, resulting in the layered morphology. This is in contrast to “normal” spherulites, where the crystal growth process leads to the formation of a radiating array of fiber crystallites. We demonstrate that COM stones consist of spherulitic domains. The domains have the shape of comparatively narrow randomly distorted cones in which the crystallites form strong texture, so that their crystallographic axes have almost the same directions and the [100] crystallographic planes are nearly perpendicular to the radial direction of the domain. However, the order among the domains does not exist. Deviations of their radial directions from the corresponding radial directions of the whole stone are not large as a rule, while the other crystallographic directions of the domains are randomly distributed. A model of layered spherulitic growth explaining the observed morphology is proposed. The model suggests that every domain is formed by means of a continuous crystallization process periodically inhibited by precipitation of organic material so that alternating organic and polycrystalline layers appear. Fine crystalline channels remaining in organic layers connect neighboring crystalline layers and maintain, thereby, the coherence of crystal structure all over the domain. Preformed COM microcrystals occasionally adsorbed from urine on the surface of the growing organic layer serve as seeds for new spherulitic domains. The results are important for understanding the general principles of biomineralization, and spherulitic crystallization and could lead to the development of new strategies for preventing kidney stone formation.

Association of body mass index and urine pH in patients with urolithiasis

Increase in body size increases the risk of renal stone formation. The mechanism explaining this relationship remains unclear. Urine pH is one of the important factors for urinary stone formation. The purpose of this study was to determine whether there is an association between urine pH and body mass index (BMI) in patients with urolithiasis. Medical charts review that included 342 urinary stone formers (248 men and 94 women). Data obtained included patient sex, age, BMI, urine pH at diagnosis, and stone composition. The patients were classified as normal weight (18.5 <or= BMI < 24), overweight (24 <or= BMI < 27), or obese (BMI >or= 27). The mean urine pH of the normal body weight, overweight, and obese groups was 6.25, 6.14, and 6.00, respectively (P < 0.05). Urine pH is inversely related to BMI among patients with urolithiasis. Among patients with urolithiasis, higher BMI will have lower urine pH. This may explain why obesity is associated with an increased risk of nephrolithiasis. Weight loss should be explored as a potential treatment to prevent kidney stone formation. The prevention of urinary stone disease gives clinicians an additional reason to encourage weight reduction through diet.

Evidence for durable kidney stone prevention over several decades

To analyse three outcomes of stone prevention strategies in one clinic devoted to that activity since 1969, i.e. stone recurrence rates, stone-related procedures and 24-h urinary stone risk factor, to assess whether such treatment can be maintained over long periods. We selected 2509 patients with at least one laboratory follow-up after initial clinical and laboratory evaluation. We divided them into five time cohorts of 5, 10, 15, 20 and >20 years of follow-up. Rates of new stones and stone-related procedures, and 24-h urinary stone risk factors were compared between the cohorts using analysis of variance and general linear modelling. Stone rates and rates of stone-related procedures declined in all five cohorts, as did 24-h urinary stone risk indices. We found no diminution of treatment effects for any of these three over time. Those patients who remained under active care had significant reductions in stone recurrence and rates of stone-related urological procedures for up to >20 years. However, only a small fraction of patients who entered the clinic remained for such long periods. Urine testing substantiates impressive and sustained reductions in supersaturation, the principle driving force for stone formation. Overall, for those patients willing to remain in continuous treatment for periods of up to three decades, medical stone prevention appears to be effective in maintaining low recurrence and procedure rates.

Prospects for Dietary Therapy of Recurrent Nephrolithiasis

The goal of this article is to propose a randomized controlled trial (RCT) that tests a hypothesis that dietary manipulation prevents recurrent kidney stones. Dietary interventions based on epidemiologic and pathophysiologic data are reviewed. The only diet trial successful in preventing stones showed that calcium intake of 1,200 mg/d, accompanied by restriction of animal protein, salt, and oxalate ingestion, was superior to 400 mg of calcium and restricted oxalate intake. This study may be worth repeating in women and in a society in which salt restriction might be less effective (eg, United States). The net result of diet trials establishes significant positive effects on urine chemistries, but these have not yet shown efficacy with regard to stone recurrence. Oxalate restriction alone could be effective, but many questions regarding which populations to study are not defined, and dietary oxalate's contribution to stone formation is disputed. Would such a study be limited to patients identified as having high dietary oxalate intake or high intestinal oxalate absorption? Would colonization with Oxalobacter formigenes influence the result? The increased prevalence of stones is linked to weight gain and obesity, making weight loss a possible therapy to prevent stones. Randomized trials show that diets consisting of low-fat content or low-caloric content cause modest weight loss and might be effective in reducing stone formation. Because the efficacy of thiazides in the prevention of stones in patients with hypercalciuria is clear, I propose dietary comparison of higher calcium intake to thiazides for the prevention of calcium-based kidney stones.

Fructose intake as a risk factor for kidney stone disease

Taylor and Curhan report that consumption of fructose is independently associated with an increased risk of incident kidney stones. What could be the mechanisms underlying the relation between fructose intake and stone risk? And how should we incorporate this finding into the dietary advice that we give to our patients to prevent kidney stone formation?

Compounds from Vitex polygama active against kidney diseases

Vitex polygama Cham. (Lamiaceae, formerly Verbenaceae) is a familiar Brazilian species popularly known as Tarumã whose leaf tea has been used by population to treat kidney diseases. The aim of this research was to investigate the hydroalcoholic extract of leaves in order to isolate the active compounds. Hydroalcoholic extract of leaves was obtained by stirring the previous hexane and methanol extracted leaves residue with 50% aqueous MeOH solution by ultra-sonic mixing. The obtained extract was partitioned with n-butanol. The yielded fraction was subsequently submitted to several chromatographic procedures to lead to the isolation of O-glycosidicflavones orientin and isoorientin as well as C-glycosylflavones schaftoside and carlinoside along with their isomers, known as potent anti-inflammatory, antinociceptive and antioxidant agents, then identified as the active constituents, justifying the folk use of the plant to combat and prevent kidney stone and inflammation.

Role of diet in the prevention of common kidney stones

AbstractThe authors discuss the evidence for the prevention of calcium stones through dietary intervention, and look at some of the emerging options. Copyright © 2007 Wiley Interface Ltd

Medical management of urinary stone disease

Kidney stones occur in ~ 10% of patients in their lifetimes, and > 10 crystal types have been reported in the literature. After treatment, a subset of these patients will have recurrent calculi, leading to significant morbidity and potential for serious chronic renal disease. Detailed metabolic evaluation is indicated in patients at high risk for stone recurrence, as a reversible metabolic abnormality can be identified in > 90% of them. Once the patient’s underlying physicochemical and physiologic derangements are defined, targeted medical therapy can be initiated in order to prevent growth of pre-existing stones and new stone formation. In this report, the author provides a comprehensive review of the presently available selective and nonselective pharmacologic treatments for stones. Several exciting investigational pharmaceutical agents for kidney stone prevention are also discussed. Although many of these agents are effective, there remain clinical scenarios in which existing medicines are insufficient.

Physiology of Acid-Base Balance: Links With Kidney Stone Prevention

Two processes permit the urine pH and the medullary interstitial pH to remain in an "ideal range" to minimize the risk of forming kidney stones. First, a medullary shunt for NH(3) maintains the urine pH near 6.0 to minimize uric acid precipitation when distal H(+) secretion is high. Second, excreting dietary alkali excreting alkali as a family of organic anions--including citrate--rather than as bicarbonate maintains the urine pH near 6.0 while urinary citrate chelates ionized calcium, which minimizes CaHPO(4) precipitation. In patients with idiopathic hypercalciuria and recurrent calcium oxalate stones, the initial nidus is a calcium phosphate precipitate on the basolateral membrane of the thin limb of the loop of Henle (Randall's plaque). Formation of this precipitate requires medullary alkalinization; K(+) -depletion and augmented medullary H(+)/K(+) -ATPase may be predisposing factors.

Renal lithiasis and nutrition

Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified trough diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins) and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine) is discussed.

Concentrated urine and diluted urine: the effects of citrate and magnesium on the crystallization of calcium oxalate induced in vitro by an oxalate load

Supplementation of certain calcium crystallization inhibitors, such as citrate and magnesium, and the dilution of urine with water are now considered consolidated practice for the prevention of calcium kidney stones. The aim of this study is to verify, using tried and true in vitro methods, whether the effect of these inhibitors can manifest itself in different ways depending on whether the urine is concentrated or diluted. Calcium oxalate crystallization was studied on 4-h urine of 20 male idiopathic calcium oxalate stone formers, first under low hydration conditions (non-diluted urine) and then under high hydration conditions (diluted urine). Both the diluted and the non-diluted urine samples were subjected to three types of load: (a) an oxalate concentration increment of 1.3 mmol/l only; (b) an oxalate concentration increment of 1.3 mmol/l with a citrate concentration increment of 1.56 mmol/l; (c) an oxalate concentration increment of 1.3 mmol/l with a magnesium concentration increment of 2.08 mmol/l. In non-diluted urine, the addition of the citrate and magnesium did not modify the crystallization parameters under study. In contrast, in the diluted urine the addition of the citrate and magnesium led to a reduction in the total quantity of crystals (equivalent to 35-45%) and their aggregates (equivalent to 30-40%); at the same time, there was an increase in the diameter of the monohydrate calcium oxalate crystals, which also underwent a morphological change. In conclusion, the inhibitory effects of citrate and magnesium on the crystallization of calcium oxalate do not manifest themselves in highly concentrated urine.

Hyperoxaluria, Hypocitraturia, Hypomagnesiuria, and Lack of Intestinal Colonization byOxalobacter formigenesin a Cervical Spinal Cord Injury Patient with Suprapubic Cystostomy, Short Bowel, and Nephrolithiasis

Although urolithiasis is common in spinal cord injury patients, it is presumed that the predisposing factors for urinary stones in spinal cord injury patients are immobilization-induced hypercalciuria in the initial period after spinal injury and, in later stages, urine infection by urease-producing micro-organisms, e.g., Proteus sp., which cause struvite stones. We describe a patient who sustained C-7 complete tetraplegia in a road traffic accident in 1970, when he was 16 years old. Left ureterolithotomy was performed in 1971 followed by left nephrectomy in 1972. Probably due to adhesions, this patient developed volvulus of the intestine in 1974. As he had complete tetraplegia, he did not feel pain in the abdomen and there was a delay in the diagnosis of volvulus, which led to ischemia of a large segment of the small bowel. All but 1 ft of jejunum and 1 ft of ileum were resected leaving the large bowel intact. In 1998, suprapubic cystostomy was performed. In 2004, this patient developed calculus in the solitary right kidney. Complete stone clearance was achieved by extracorporeal shock wave lithotripsy. Stone analysis: calcium oxalate 60% and calcium phosphate 40%. Metabolic evaluation revealed hyperoxaluria, hypocitraturia, and hypomagnesiuria. Since this patient had hyperoxaluria, the stool was tested for Oxalobacter formigenes, a specific oxalate-degrading, anerobic bacterium inhabiting the gastrointestinal tracts of humans; absence of this bacterium appears to be a risk factor for development of hyperoxaluria and, subsequently, calcium oxalate kidney stone disease. DNA from the stool was extracted using the QIAamp DNA stool Mini Kit (Qiagen, Chatsworth, CA). The genomic DNA was amplified by polymerase chain reaction using specific primers for oxc gene (developed by Sidhu and associates). The stool sample tested negative for O. formigenes. The patient was prescribed potassium citrate mixture; he was advised to avoid oxalate-rich food, maintain recommended levels of calcium in his diet, and take live bio-yogurt. Two months later, 24-h urinary oxalate decreased from 0.618 to 0.411 mmol/day; 24-h urine citrate increased from 0.58 to 1.10 mmol/day. Six months later, an oxalate absorption test was performed. The patient swallowed a capsule, soluble in gastric juice, containing 50 mg (0.37 mmol) sodium [13C2]oxalate corresponding to 33.8 mg of [13C2]oxalic acid. The amount of labeled oxalate, excreted in urine, was measured by a gas chromatographic-mass spectrometric assay. Oxalate absorption, expressed as the percentage of the labeled dose recovered in the 24-h urine after dosing, was 8.3% (reference range: 2.3–17.5%). In addition to other conventional measures, oral administration of O. formigenes or lactic acid bacteria mixture to promote bacterial degradation of oxalate in the gut, and thus combat hyperoxaluria, may play a role in prevention of calcium oxalate kidney stones.

Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria

In order to prevent kidney stones and nephrolithiasis in hyperoxaluria, a new treatment that specifically reduces oxalate production and therefore urinary oxalate excretion would be extremely valuable. Pyridoxamine(PM) could react with the carbonyl intermediates of oxalate biosynthesis, glycolaldehyde and glyoxylate, and prevent their metabolism to oxalate. In PM treated rats, endogenous urinary oxalate levels were consistently lower and became statistically different from controls after 12 days of experiment. In ethylene glycol-induced hyperoxaluria, PM treatment resulted in significantly lower (by ~50%) levels of urinary glycolate and oxalate excretion compared to untreated hyperoxaluric animals, as well as in a significant reduction in calcium oxalate crystal formation in papillary and medullary areas of the kidney. These results, coupled with favorable toxicity profiles of PM in humans, show promise for the therapeutic use of PM in primary hyperoxaluria and other kidney stone diseases.

SPECIAL COLLECTION: DOGMAS AND CONTROVERSIES IN THE HANDLING OF NITROGENOUS WASTES

Science is full of dogmas. But during the process of discovery, some dogmas face challenges, and the dogmas in nitrogen waste management are no different. As all biology students know, the dogma holds that waste proteins are broken down and excreted from the body in a variety of forms, such as

History of kidney stones as a possible risk factor for chronic kidney disease.

The incidence of treated end-stage renal disease has increased progressively in the United States over the past several decades. It has been suggested that kidney stones may be a contributing factor for a small percentage of these patients. We conducted a case-control study utilizing 548 hospital cases and 514 age, race and gender-matched community controls. The main outcome measure was diagnosis of chronic kidney disease, assessed by comprehensive chart review. History of kidney stones and other co-variables were obtained during telephone interviews. This study revealed 16.8% of cases and 6.4% of controls with reported history of kidney stones. The odds ratios (adjusted for confounding variables) for chronic kidney disease (overall), diabetic nephropathy and interstitial nephritis for patients with kidney stones were 1.9 (95% CI: 1.1, 3.3), 2.5 (95% CI: 0.87, 7.0) and 3.4 (95% CI: 1.5, 7.4), respectively. After stratifying by hypertensive status this increased risk persisted only for study participants reporting no history of hypertension. Kidney stones may play a role in the development of chronic kidney disease. Our study suggests that the prevention of kidney stones may be a means of delaying the onset of chronic kidney disease, however, further studies are needed to make conclusive recommendations.

Outcome Of Metabolic Evaluation and Medical Treatment for Calcium Nephrolithiasis in a Private Urological Practice

We determine if medications that have been proven effective for kidney stone prevention in prospective controlled trials can reduce kidney stone recurrence in a private practice of urology better than life-style advice, including hydration. Between July 1, 1995 and December 31, 1996, 203 patients with stones received care from 1 private practice. Physicians chose to evaluate these patients metabolically based on clinical judgement. Thiazide, potassium citrate and allopurinol are recognized in this study as active treatments, and drug treatment intervals were calculated. Relapse and recurrent stones were counted as those stones manifesting after the initial index event. A stone was called a relapse stone if its date was included in the active treatment interval. The association between use of active therapy and ordering of metabolic evaluation was highly significant. Using survival tables, we separately considered all patients and only those who had formed more than 1 stone. For both populations active treatment reduced stone recurrence significantly more than diet advice and hydration. Medications validated in trials and guided by metabolic evaluation lower stone recurrence when used in a private practice setting as they do in trials.

Intracrystalline Proteins and Urolithiasis: A Synchrotron X-ray Diffraction Study of Calcium Oxalate Monohydrate

The existence of intracrystalline proteins and amino acids in calcium oxalate monohydrate was demonstrated by X-ray synchrotron diffraction studies. Their presence has implications for the destruction of calcium oxalate crystals formed in the urinary tract and the prevention of kidney stones. Although proteins are present in human kidney stones, their role in stone pathogenesis remains unknown. This investigation aimed to characterize the nature of the relationship between the organic and mineral phases in calcium oxalate monohydrate (COM) crystals grown in human urine and in aqueous solutions of proteins and amino acids to clarify the function of proteins in urolithiasis. COM crystals were grown in human urine and in aqueous solutions containing either human prothrombin (PT), Tamm-Horsfall glycoprotein (THG), aspartic acid (Asp), aspartic acid dimer (AspAsp), glutamic acid (Glu), glutamic acid dimer (GluGlu), or gamma-carboxyglutamic acid (Gla). Controls consisted of COM crystals precipitated from pure inorganic solutions or from human urine that had been ultrafiltered to remove macromolecules. Synchrotron X-ray diffraction with Rietveld whole-pattern peak fitting and profile analysis was used to determine nonuniform crystal strain and crystallite size in polycrystalline samples. Crystals precipitated from ultrafiltered urine had lower nonuniform strain than those grown in urine or in aqueous PT solution. Nonuniform strain was much lower in crystals grown in distilled water or in the presence of THG. For the amino acids, the highest nonuniform strain was exhibited by crystals grown in Gla solution, followed by Glu. Crystallite size was inversely related to nonuniform strain, with the effect being significantly less for amino acids than for macromolecules. Selected proteins and amino acids associated with COM crystals are intracrystalline. Although their incorporation into the mineral bulk would be expected to affect the rate of crystal growth, they also have the potential to influence the phagocytosis and intracellular destruction of any crystals nucleated and trapped within the renal collecting system. Crystals impregnated with protein would be more susceptible to digestion by cellular proteases, which would provide access to the crystal core, thereby facilitating further proteolytic degradation and mineral dissolution. We therefore propose that intracrystalline proteins may constitute a natural form of defense against renal stone formation.

Kidney Stones, Carbonic Anhydrase Inhibitors, and the Ketogenic Diet

To the Editor: I read with interest the article by Kossoff et al. (1) concerning kidney stones. I understand the limitations of their study and agree with the recommendation of increased hydration for prevention of kidney stones in children at high risk for stone formation with ketogenic diet and carbonic anhydrase inhibitors. However, the recommendation for urine alkalinization in these children receiving combination therapy is supported neither by the pathophysiology nor by their findings. Combination therapy had a slightly lower risk, although not clinically significant, of stone formation compared with the ketogenic diet alone. Unfortunately, stone analysis was not performed. Ketogenic diet leads to urinary acidification, hypocitruria, and hypercalciuria, and thereby increases the risk of uric acid stones compared with calcium phosphate and oxalate stones. Carbonic anhydrase inhibitors instead alkalinize the urine weakly and may negate the effect of the ketogenic diet by counteracting urinary acidification. We know acidic urine promotes uric acid precipitation, whereas alkaline urine results in calcium phosphate precipitation. Carbonic anhydrase inhibitors, by alkalinizing urine, potentiate calcium phosphate stone (2) formation, and further alkalinizing the urine in these children would aggravate calcium phosphate stone formation. Adequate hydration should be maintained in children at high risk for stone formation receiving the combination of ketogenic diet and carbonic anhydrase inhibitors, and alkalinization of urine should be considered for children on the ketogenic diet alone.

Preventing kidney stones: calcium restriction not warranted.

The traditional wisdom on preventing calcium stones, the most common form of kidney stone, has been to advise patients to limit dietary calcium. Research has proved this wrong, however. Normal dietary calcium intake, along with reduced salt and protein, is now advised. This paper also summarizes the diagnosis and treatment of the less-common forms of kidney stones-struvite, uric acid, and cystine.

PATIENT ADHERENCE TO LONG-TERM MEDICAL TREATMENT OF KIDNEY STONES

We determine patient adherence to and quality of outcome of medical kidney stone treatment during a 30-year duration at a single university based referral clinic. We also analyze time trends in adherence and timing of followup measurements, and supersaturation reduction during treatment. Data on all patients who entered the University of Chicago Kidney Stone Prevention Program from 1970 to 2000 were analyzed. Fractions of new patients who had any followup and those remaining in followup at increasing intervals were analyzed. Timing of followup was measured. Changes in adherence during the 3 decades were also analyzed, as was reduction in supersaturation in regard to calcium oxalate, calcium phosphate and uric acid. A total of 70% to 80% of patients were retained at each successive followup cycle with 2 physicians, and a clinical protocol that always required 6-week followup with 24-hour urine collection and a yearly one thereafter for stone risk factors. Retention decreased during the last 5 years of the 1990s. Supersaturation reduction was present by the first followup and remained constant or improved with time. Timing of followup measurements was in accord with our protocol. At best, one can retain only 70% to 80% of patients in a followup program at each interval, and achieve supersaturation reductions that are constant and significant during the long term. Timing of followup measurements can be close to that of the protocol in use.